DANTRIUM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DANTRIUM (DANTRIUM).
Dantrolene inhibits calcium release from the sarcoplasmic reticulum by binding to the ryanodine receptor (RyR1), thereby reducing intracellular calcium concentration and decreasing muscle contraction.
| Metabolism | Metabolized in the liver via microsomal enzymes (CYP3A4 and others) to 5-hydroxydantrolene (active metabolite) and other metabolites. Undergoes enterohepatic recirculation. |
| Excretion | Renal: ~65% as unchanged drug; biliary/fecal: ~15% as metabolites; remainder metabolized and eliminated via urine. |
| Half-life | Terminal elimination half-life: 8.7-14.4 hours in adults; longer with hepatic dysfunction. |
| Protein binding | ~90% bound to albumin. |
| Volume of Distribution | Vd: 0.8-1.2 L/kg; suggests extensive tissue distribution. |
| Bioavailability | Oral: ~70% (first-pass metabolism reduces from ~90% absorbed). |
| Onset of Action | IV: 2-4 minutes; Oral: 1-2 hours. |
| Duration of Action | IV: 30-60 minutes; Oral: 4-6 hours; prolonged in hepatic impairment. |
Initially 25 mg orally once daily for 7 days, then 25 mg three times daily for 7 days, then 50 mg three times daily for 7 days, then 100 mg three times daily; maximum 400 mg/day in divided doses. For malignant hyperthermia crisis: IV bolus 1 mg/kg, repeated as needed up to 10 mg/kg cumulative dose.
| Dosage form | CAPSULE |
| Renal impairment | No specific guidelines; use with caution in renal impairment due to potential accumulation. Monitor renal function and reduce dose if toxicity occurs. |
| Liver impairment | Contraindicated in active hepatic disease (elevated AST/ALT, hepatitis, cirrhosis). For Child-Pugh A: reduce dose by 50%; Child-Pugh B: reduce dose by 75%; Child-Pugh C: avoid use. |
| Pediatric use | Spasticity: 0.5 mg/kg/dose twice daily, titrate up to 0.5-2 mg/kg/dose three times daily; maximum 100 mg four times daily for children >5 years. Malignant hyperthermia: IV 1 mg/kg, repeated as needed. |
| Geriatric use | Start at lower end of dosing range (25 mg daily), titrate slowly. Increased risk of sedation, muscle weakness, and hepatic toxicity. Monitor liver function frequently. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DANTRIUM (DANTRIUM).
| Breastfeeding | Dantrolene is excreted in breast milk at low levels; M/P ratio is approximately 0.5 based on limited data. Theoretical risk of muscle weakness and CNS effects in nursing infants. Caution advised; monitor infant for sedation, hypotonia, or feeding difficulties. Consider alternative therapy if possible. |
| Teratogenic Risk | Dantrolene (Dantrium) is classified as FDA Pregnancy Category C. Animal studies have shown an increased incidence of fetal resorptions and delayed ossification at doses ≥ 30 mg/kg/day in rats and 45 mg/kg/day in rabbits. There are no adequate and well-controlled studies in pregnant women. Potential risks include skeletal anomalies and embryotoxicity. Use only if potential benefit justifies potential risk to fetus. |
■ FDA Black Box Warning
Hepatotoxicity: Dantrolene can cause fatal hepatitis, especially with long-term use (≥60 days) and at doses >300 mg/day. Liver function must be monitored before and during therapy. Risk is increased in females, patients >35 years, and those on other hepatotoxic medications.
| Serious Effects |
["Active hepatic disease (e.g., hepatitis, cirrhosis)","Patients in whom muscle weakness is undesirable (e.g., myasthenia gravis, amyotrophic lateral sclerosis)","Hypersensitivity to dantrolene or any component of the formulation","Breastfeeding (discontinue or do not breastfeed; potential for serious adverse reactions in infants)"]
| Precautions | ["Monitor liver function tests (LFTs) before and during therapy; discontinue if hepatic injury suspected.","May cause muscle weakness, impair ability to drive or operate machinery.","Caution in patients with compromised respiratory function or impaired cardiac function due to negative inotropic effects.","Photosensitivity reactions possible.","Risk of pleural effusion and pericarditis with long-term use.","Use with caution in renal impairment (no dosage adjustment needed, but monitor)."] |
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| Fetal Monitoring | Monitor liver function tests (LFTs) periodically due to risk of hepatotoxicity. Assess for signs of muscle weakness, respiratory depression, or extrapyramidal effects in mother. In pregnancy, fetal monitoring with ultrasound for growth and development if exposure during first trimester. Non-stress testing if late pregnancy exposure. |
| Fertility Effects | No specific human data; animal studies suggest no significant impact on fertility at clinically relevant doses. However, dantrolene may cause testicular atrophy in male rats at high doses; relevance unknown. Effects on female fertility not well studied. |